Brief Communications Ciliary Motility in Two Patients with Yellow Nail Syndrome and Recurrent Sinopulmonary Infections1.2
ADELAIDA M. MIRO, VISWANATH VASUDEVAN, and HEMANT SHAH
The yellow nail syndrome (YNS) is a rare disorder classically described as a triad of yellow nails, lymphedema, and pleural effusions (1). Recurrent sinusitis, bronchitis, and bronchiectasis leading to recurrent pneumonias are commonly associated features and have been added as part of this syndrome. However, YNS may occur with any combination of these features, even in the absence of yellowish discoloration of nails (2). Immunologic deficienciessuch as lymphopenia or hypogammaglobulinemia have been found in conjunction with YNS and are thought to predispose a person to recurrent sinopulmonary infections (3). This association, however, is not universally present. In conditions where mucociliary defenses of the respiratory system are impaired, as with primary ciliary dyskinesia, frequent infections are common (4). Because the airways are richly supplied by lymphatic vessels, it seems possible that lymphatic stasis could modify the local milieu such that mucociliary transport would be altered. Such alterations in transport could account for the propensity to upper and lower respiratory infections seen with YNS. To the best of our knowledge, no aspect ofmucociliary function in YNS has been previously studied. We have examined the ciliary activity in two patients with YNS and recurrent sinopulmonary infections. Two patients with YNS were evaluated in this study. In both patients, the diagnosis of YNS was made on the basis of typical clinical features and after exclusion of other diseases (table 1). Leukocyte, lymphocyte, and neutrophil counts together with immunoglobulin levels were obtained. Ciliary motility was evaluated by measuring the ciliary beat frequency (CBF) from nasal mucosal brushings obtained by introducing a cytologic brush catheter into the posterior nares. Specimens recovered were immediately immersed in nutrient medium 199(GIBCO, Grand Island, NY), and measurements were performed within 1 h. The in vitro CBF was determined by the method of Yager and coworkers (5), which involves placing the specimen on the stage of an interference contrast microscope (E. Leitz, Inc., Rockleigh, NJ) where variations in light intensity, created by the corresponding CBF, are detected by a photomultiplier, amplified, and displayed on a storage oscilloscope. The frequency of the electric signal corresponds to the frequency of ciliary beating. Excessive mucus was carefully
890
SUMMARY The yellow nail syndrome (YNS) is described as a combination of yellow nails, chronic lymphedema, pleural effusions, and recurrent sinopulmonary infections, but all these features need not be present for the diagnosis. The mechanism that renders patients with this syndrome susceptible to respiratory infections is not known. To determine whether abnormal ciliary motility is a predisposing factor, in vitro ciliary beat frequency (CBF) was measured in two patients with YNS and recurrent respiratory infections. In each case, the CBF was within normal limits (12 Hz). These data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulAM REV RESPIR DIS 1990; 142:890-891 monary infections in YNS.
removed with forceps or a needle and specimens were maintained at a temperature of 37° C by a Sage electric air curtain (Orion Research Inc., Cambridge, MA). Ten consecutive measurements were made of different strips of ciliated cells from the same nasal specimen and the mean value was obtained.
The manifestations of YNS and the associated respiratory tract involvement in each subject are summarized in table 1. Patient 1 had the classic triad of yellow nails, lymphedema, and pleural effusions and was the same individual previously reported by Dwek and Greenberg (6). Patient 2 had the characteristic nail changes and chronic lower extremity lymphedema but no evidence of pleural effusions. Both patients had documented recurrent upper and lower respiratory tract infections and were lifelong nonsmokers. Neither patient had evidence of leukopenia, lymphopenia, or hypogammaglobulinemia. In both cases, the in vitro CBF was found to be 12 ± 0.6 and 12 ± 0.4 Hz, respectively, which are within the normal limits set by our laboratory (table 2).
* * * Respiratory infections such as sinusitis, bronchitis, and bronchiectasis leading to pneumonia have been described frequently in patients with YNS (7, 8). The propensity for infectious complications has been attributed to leukopenia, lymphopenia, hypogammaglobulinemia, isolated immunoglobulin A and immunoglobulin M deficiencies secondary to intestinalloss, or pleural sequestration from dilated lymphatics (8). Additional support for an immunologic aberration in YNS is the association with autoimmune diseases and malignancies (3, 7, 9). Although these findings may explain the predisposition to infee-
tious respiratory complications in certain patients, in many cases in the literature, and in both our subjects, no quantitative systemic immunologic derangement was found. A normal CBF in both our patients demonstrated that lymphatic stasis did not alter in vitrociliary motility in this disease. In examining ciliary function, nasal mucosal brushings weresampled for CBF determinations because previous studies have shown that nasal cilia possess the same CBF as specimens obtained from tracheal and bronchial mucosa (10). Rutland and colleagues (11) reported this sampling method as a reliable screening tool that accurately detected abnormalities in both ciliary structure and motility. Although ciliary ultrastructure was not examined, data from previous studies have shown that a significant abnormality is unlikely to translate into a normal beating frequency (12). Thus, our data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulmonary infections in this disorder. Alternate factors that may impair in vivo mucociliary clearance without an innate ciliary defect in function are a decrease in the total number of ciliated cells, an increase in
(Received in original form July 14, 1989 and in revised form May 10, 1990) 1 From the Pulmonary Division, Department of Internal Medicine, Woodhull Medical and Mental Health Center, State University of New York Health Science Center at Brooklyn, Brooklyn, New York. 2 Correspondence and requests for reprints should be addressed to Adelaida M. Miro, M.D., Presbyterian University Hospital, Division of Critical Care Medicine, Department of Anesthesiology, DeSoto at O'Hara Streets, Pittsburgh, PA 15213.
891
BRIEF COMMUNICATION
TABLE 1 PATIENT CHARACTERISTICS Patient 1
Patient 2
65
29
F
F
Age, yr Sex
References
Features of YNS
Yellow nails Lymphedema Pleural effusion
Yellow nails Lymphedema
Associated respiratory disorders
Sinusitis Chronic bronchitis Pneumonia Bronchiectasis
Sinusitis Chronic bronchitis Pneumonia
28
4
Duration of YNS, yr
Definition of abbreviation: YNS = yellow nail syndrome.
TABLE 2 IMMUNOLOGIC AND CILIARY BEAT FREQUENCY DETERMINATIONS
Leukocytes, per mm" Lymphocytes, per rnm" Neutrophils, per rnrn" Immunoglobulin levels IgG (nl = 700 to 1,800) IgM (nl = 60 to 290) IgA (nl = 70 to 440) Ciliary beat frequency, Hz ± SD
mucus secreting cells, areas of squamous metaplasia, abnormalities in the viscoelastic properties of mucus, or the presence of ciliotoxic factors (13). Despite significant morbidity in patients with YNS, long-term prognosis appears favorable, as exemplified by Patient 1who has been followed since 1963 with chronic bilateral pleural effusions and occasional bouts of acute bronchitis that were managed with oral antibiotics. Tothe best of our knowledge, this is the longest interval in which a case of YNS has been prospectively followed. In summary, the mechanism by which the
Patient 1
Patient 2
8,400 1,420 6,552
12,000 1,920 7,680
1,286
1,877 478 196 12 ± 0.4
63 291 12 ± 0.6
ministration Medical Center for performing the ciliary beat frequency determinations, and Dr. Stephan L. Kamholz for his critical review of the manuscript.
YNS renders a host susceptible to respiratory tract infections remains unknown. Because this is an extremely uncommon and heterogenous entity, there have been no large studies to delineate its pathophysiology, and we are left with piecemeal acquisitions of information. Only rarely is systemic immunity deficient, and local defenses such as ciliary activity appear intact based on the two patients reported.
Acknowledgment The writers thank Oscar Wooten and the Sputum Laboratory at the Brooklyn VeteransAd-
r-n
1. Samman White WE The "yellow nail" syndrome. Br J Dermatol 1964; 76:153-7. 2. Pavlidakey GP, Hashimoto K, Blum D. Yellow nail syndrome. J Am Acad Dermatol 1984; 11: 509-12. 3. Siegelman SS, Heckman BH, Hasson J. Lymphedema, pleural effusions and yellow nails: associated immunologic deficiency. Dis Chest 1969; 56:114-7. 4. Pederson M, Stafanger G. Bronchopulmonary symptoms in primary ciliary dyskinesia: a clinical study of 27 patients. Eur J Respir Dis 1983; 64 (Suppl 127:118-28). 5. Yager J, Chen TM, Dulfano MJ. Measurement of frequency of ciliary beats of human respiratory epithelium. Chest 1978; 73:627-33. 6. Dwek JH, Greenberg GM. Yellow nails, lymphedema, and pleural effusions. NY State J Med 1973; 73:1093-7. 7. Hiller E, Rosenow EC, Olsen AM. Pulmonary manifestations of the yellow nail syndrome. Chest 1972; 61:452-8. 8. Venencie PY, Dicken CH. Yellow nail syndrome: report of five cases. J Am Acad Dermatol 1984; 10:187-92. 9. Guin JD, Elleman JH. Yellow nail syndrome: possible association with malignancy. Arch Dermatol 1979; 115:734-5. 10. Yager J, Chen TM, Dulfano MJ. Human ciliary beat frequency at three levels of the tracheobronchial tree. Am Rev Respir Dis 1980; 121:661-6. 11. Rutland J, Cox T, Dewar A, Cole P. Screening for ciliary dvskinesia: a spectrum of defects of motility and structure. Eur J Respir Dis 1983;64(Suppl 127:71-7). 12. Rossman CM, Lee RMKW, Forrest JB, Newhouse MT. Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases. Am Rev Respir Dis 1984; 129:161-7. 13. Levinson H, Mindorff CM, Chao J, Turner JAP, Sturgess JM, Stringer DA. Pathophysiology of the ciliary motility syndromes. Eur J Respir Dis 1983; 64(Suppl 127:102-16).
ADELAIDA M. MIRO, VISWANATH VASUDEVAN, and HEMANT SHAH
The yellow nail syndrome (YNS) is a rare disorder classically described as a triad of yellow nails, lymphedema, and pleural effusions (1). Recurrent sinusitis, bronchitis, and bronchiectasis leading to recurrent pneumonias are commonly associated features and have been added as part of this syndrome. However, YNS may occur with any combination of these features, even in the absence of yellowish discoloration of nails (2). Immunologic deficienciessuch as lymphopenia or hypogammaglobulinemia have been found in conjunction with YNS and are thought to predispose a person to recurrent sinopulmonary infections (3). This association, however, is not universally present. In conditions where mucociliary defenses of the respiratory system are impaired, as with primary ciliary dyskinesia, frequent infections are common (4). Because the airways are richly supplied by lymphatic vessels, it seems possible that lymphatic stasis could modify the local milieu such that mucociliary transport would be altered. Such alterations in transport could account for the propensity to upper and lower respiratory infections seen with YNS. To the best of our knowledge, no aspect ofmucociliary function in YNS has been previously studied. We have examined the ciliary activity in two patients with YNS and recurrent sinopulmonary infections. Two patients with YNS were evaluated in this study. In both patients, the diagnosis of YNS was made on the basis of typical clinical features and after exclusion of other diseases (table 1). Leukocyte, lymphocyte, and neutrophil counts together with immunoglobulin levels were obtained. Ciliary motility was evaluated by measuring the ciliary beat frequency (CBF) from nasal mucosal brushings obtained by introducing a cytologic brush catheter into the posterior nares. Specimens recovered were immediately immersed in nutrient medium 199(GIBCO, Grand Island, NY), and measurements were performed within 1 h. The in vitro CBF was determined by the method of Yager and coworkers (5), which involves placing the specimen on the stage of an interference contrast microscope (E. Leitz, Inc., Rockleigh, NJ) where variations in light intensity, created by the corresponding CBF, are detected by a photomultiplier, amplified, and displayed on a storage oscilloscope. The frequency of the electric signal corresponds to the frequency of ciliary beating. Excessive mucus was carefully
890
SUMMARY The yellow nail syndrome (YNS) is described as a combination of yellow nails, chronic lymphedema, pleural effusions, and recurrent sinopulmonary infections, but all these features need not be present for the diagnosis. The mechanism that renders patients with this syndrome susceptible to respiratory infections is not known. To determine whether abnormal ciliary motility is a predisposing factor, in vitro ciliary beat frequency (CBF) was measured in two patients with YNS and recurrent respiratory infections. In each case, the CBF was within normal limits (12 Hz). These data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulAM REV RESPIR DIS 1990; 142:890-891 monary infections in YNS.
removed with forceps or a needle and specimens were maintained at a temperature of 37° C by a Sage electric air curtain (Orion Research Inc., Cambridge, MA). Ten consecutive measurements were made of different strips of ciliated cells from the same nasal specimen and the mean value was obtained.
The manifestations of YNS and the associated respiratory tract involvement in each subject are summarized in table 1. Patient 1 had the classic triad of yellow nails, lymphedema, and pleural effusions and was the same individual previously reported by Dwek and Greenberg (6). Patient 2 had the characteristic nail changes and chronic lower extremity lymphedema but no evidence of pleural effusions. Both patients had documented recurrent upper and lower respiratory tract infections and were lifelong nonsmokers. Neither patient had evidence of leukopenia, lymphopenia, or hypogammaglobulinemia. In both cases, the in vitro CBF was found to be 12 ± 0.6 and 12 ± 0.4 Hz, respectively, which are within the normal limits set by our laboratory (table 2).
* * * Respiratory infections such as sinusitis, bronchitis, and bronchiectasis leading to pneumonia have been described frequently in patients with YNS (7, 8). The propensity for infectious complications has been attributed to leukopenia, lymphopenia, hypogammaglobulinemia, isolated immunoglobulin A and immunoglobulin M deficiencies secondary to intestinalloss, or pleural sequestration from dilated lymphatics (8). Additional support for an immunologic aberration in YNS is the association with autoimmune diseases and malignancies (3, 7, 9). Although these findings may explain the predisposition to infee-
tious respiratory complications in certain patients, in many cases in the literature, and in both our subjects, no quantitative systemic immunologic derangement was found. A normal CBF in both our patients demonstrated that lymphatic stasis did not alter in vitrociliary motility in this disease. In examining ciliary function, nasal mucosal brushings weresampled for CBF determinations because previous studies have shown that nasal cilia possess the same CBF as specimens obtained from tracheal and bronchial mucosa (10). Rutland and colleagues (11) reported this sampling method as a reliable screening tool that accurately detected abnormalities in both ciliary structure and motility. Although ciliary ultrastructure was not examined, data from previous studies have shown that a significant abnormality is unlikely to translate into a normal beating frequency (12). Thus, our data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulmonary infections in this disorder. Alternate factors that may impair in vivo mucociliary clearance without an innate ciliary defect in function are a decrease in the total number of ciliated cells, an increase in
(Received in original form July 14, 1989 and in revised form May 10, 1990) 1 From the Pulmonary Division, Department of Internal Medicine, Woodhull Medical and Mental Health Center, State University of New York Health Science Center at Brooklyn, Brooklyn, New York. 2 Correspondence and requests for reprints should be addressed to Adelaida M. Miro, M.D., Presbyterian University Hospital, Division of Critical Care Medicine, Department of Anesthesiology, DeSoto at O'Hara Streets, Pittsburgh, PA 15213.
891
BRIEF COMMUNICATION
TABLE 1 PATIENT CHARACTERISTICS Patient 1
Patient 2
65
29
F
F
Age, yr Sex
References
Features of YNS
Yellow nails Lymphedema Pleural effusion
Yellow nails Lymphedema
Associated respiratory disorders
Sinusitis Chronic bronchitis Pneumonia Bronchiectasis
Sinusitis Chronic bronchitis Pneumonia
28
4
Duration of YNS, yr
Definition of abbreviation: YNS = yellow nail syndrome.
TABLE 2 IMMUNOLOGIC AND CILIARY BEAT FREQUENCY DETERMINATIONS
Leukocytes, per mm" Lymphocytes, per rnm" Neutrophils, per rnrn" Immunoglobulin levels IgG (nl = 700 to 1,800) IgM (nl = 60 to 290) IgA (nl = 70 to 440) Ciliary beat frequency, Hz ± SD
mucus secreting cells, areas of squamous metaplasia, abnormalities in the viscoelastic properties of mucus, or the presence of ciliotoxic factors (13). Despite significant morbidity in patients with YNS, long-term prognosis appears favorable, as exemplified by Patient 1who has been followed since 1963 with chronic bilateral pleural effusions and occasional bouts of acute bronchitis that were managed with oral antibiotics. Tothe best of our knowledge, this is the longest interval in which a case of YNS has been prospectively followed. In summary, the mechanism by which the
Patient 1
Patient 2
8,400 1,420 6,552
12,000 1,920 7,680
1,286
1,877 478 196 12 ± 0.4
63 291 12 ± 0.6
ministration Medical Center for performing the ciliary beat frequency determinations, and Dr. Stephan L. Kamholz for his critical review of the manuscript.
YNS renders a host susceptible to respiratory tract infections remains unknown. Because this is an extremely uncommon and heterogenous entity, there have been no large studies to delineate its pathophysiology, and we are left with piecemeal acquisitions of information. Only rarely is systemic immunity deficient, and local defenses such as ciliary activity appear intact based on the two patients reported.
Acknowledgment The writers thank Oscar Wooten and the Sputum Laboratory at the Brooklyn VeteransAd-
r-n
1. Samman White WE The "yellow nail" syndrome. Br J Dermatol 1964; 76:153-7. 2. Pavlidakey GP, Hashimoto K, Blum D. Yellow nail syndrome. J Am Acad Dermatol 1984; 11: 509-12. 3. Siegelman SS, Heckman BH, Hasson J. Lymphedema, pleural effusions and yellow nails: associated immunologic deficiency. Dis Chest 1969; 56:114-7. 4. Pederson M, Stafanger G. Bronchopulmonary symptoms in primary ciliary dyskinesia: a clinical study of 27 patients. Eur J Respir Dis 1983; 64 (Suppl 127:118-28). 5. Yager J, Chen TM, Dulfano MJ. Measurement of frequency of ciliary beats of human respiratory epithelium. Chest 1978; 73:627-33. 6. Dwek JH, Greenberg GM. Yellow nails, lymphedema, and pleural effusions. NY State J Med 1973; 73:1093-7. 7. Hiller E, Rosenow EC, Olsen AM. Pulmonary manifestations of the yellow nail syndrome. Chest 1972; 61:452-8. 8. Venencie PY, Dicken CH. Yellow nail syndrome: report of five cases. J Am Acad Dermatol 1984; 10:187-92. 9. Guin JD, Elleman JH. Yellow nail syndrome: possible association with malignancy. Arch Dermatol 1979; 115:734-5. 10. Yager J, Chen TM, Dulfano MJ. Human ciliary beat frequency at three levels of the tracheobronchial tree. Am Rev Respir Dis 1980; 121:661-6. 11. Rutland J, Cox T, Dewar A, Cole P. Screening for ciliary dvskinesia: a spectrum of defects of motility and structure. Eur J Respir Dis 1983;64(Suppl 127:71-7). 12. Rossman CM, Lee RMKW, Forrest JB, Newhouse MT. Nasal ciliary ultrastructure and function in patients with primary ciliary dyskinesia compared with that in normal subjects and in subjects with various respiratory diseases. Am Rev Respir Dis 1984; 129:161-7. 13. Levinson H, Mindorff CM, Chao J, Turner JAP, Sturgess JM, Stringer DA. Pathophysiology of the ciliary motility syndromes. Eur J Respir Dis 1983; 64(Suppl 127:102-16).
![[Yellow nail syndrome: two pediatric case reports].](/assets/img/hold.png)
